Correlação entre fenótipo e genótipo de pacientes com doença de Stargardt

• Autor(a) principal: Salles, Mariana Vallim [UNIFESP]
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6748145; https://repositorio.unifesp.br/handle/11600/52904
• topic: Retinitis pigmentosa; Retina; Stargardt disease; Genetic disease; DNA; Retinose pigmentar; Retina; Doença de Stargardt; Doença genética; Analise de DNA

Purpose: To identify genetic variants in Brazilian patients with clinical diagnosis of Stargardt disease and to correlate with its phenotypic manifestation and hereditary characteristics. Methods: Patients with clinical diagnosis of Stargardt disease from retina clinic of UNIFESP were included. Medical records from patients from the Instituto de Genética Ocular, São Paulo – Brazil, were reviewed. The ABCA4, ELOVL4 and PROM1 genes were analyzed by the nextgeneration sequencing (NGS) and complementation with the Sanger sequencing. Results: 52 patients from 47 families were included. In the first phase 24 patients from 21 families from retina clinic of UNIFESP were selected. In the second phase, 254 medical records from Instituto de Genética Ocular were reviewed. Of these, 28 patients from 26 families with pathogenic variants in the ABCA4 and PROM1 genes detected by NGS were selected. No patient had genetic alteration in the ELOVL4 gene. The age of the patients varied from 10 to 66 years and the age of onset of symptoms was on average 14 years of age (ranged from 5 to 40 years of age). A visual acuity ranged from 20/40 to 20 cm at the time of examination. Retinal flecks was found in the retina examination and was associated with macular atrophy. The ABCA4 gene sequencing was conclusive in 41 patients, inconclusive in 8 and negative in 1 case. Two patients have their phenotypic characteristics due to the presence of variants in the PROM1 gene. This study described 5 new pathogenic variants and 3 new complex alleles in the ABCA4 gene. Conclusion: The NGS gene panel was effective to conclude the diagnosis in approximately 80% of the patients. Despite wide genetic and clinic variability, there was concordance in sibling disease expression with the same genotype. The identification of the complex alleles in 14 families (30% of cases) reinforces the importance of the segregation test for the conclusion of the molecular diagnosis related to the ABCA4 gene.